Summary of Work: We continue to analyze data from a case-control study of risk factors for the acute leukemias and the myelodysplastic syndromes. We have confirmed associations between smoking and specific cytogenetic abnormalities in acute myeloid leukemia in a second case group. In addition, we have completed our analysis of risk factors for the myelodysplastic syndromes, a collection of hematologic disorders of increasing importance among the elderly. In our study of 158 adults with myelodysplasia and population controls, smoking and hair dye use were associated with increased risk. Occupational exposures were also associated with MDS, including petroleum distillates, halogenated solvents, welding fumes and other agents. In contrast, these factors were not associated with AML that was not preceded by myelodysplasia unless specific chromosome abnormalities were present. These results suggest that myelodysplasia may be a marker of chemical exposure in AML. We are continuing to explore the role of genes that affect the metabolism of specific carcinogens. We previously showed that persons with the null genotype of the glutathione-S-transferase theta gene had four times the odds of developing myelodysplastic syndromes as persons with the gene, although no clear exposure-gene interactions were identified and are now exploring the role of other genes. We have also attempted to replicate our preliminary finding of a strong association between ras gene mutations in AML and solvent exposure. However, results on a larger sample of patients do not confirm this observation. Planning for new molecular and epidemiologic studies of these conditions continues.